Ovarian cancer is a type of solid tumour that begins in the ovaries. Ovarian cancer symptoms are mistaken for more-common conditions and so with late diagnosis, cure is not possible. The treatment of ovarian cancer is based on the stage of the disease which is a reflection of the extent or spread of the cancer to other parts of the body. The stages of cancer are explained as below:
Stage I: If the cancer is confined to one or both ovaries.
Stage II: If either one or both of the ovaries are involved and the tumour has spread to the uterus and/or the fallopian tubes or other sites in the pelvis.
Stage III: If one or both of the ovaries are involved and the tumour has spread to lymph nodes or other sites such as outside the pelvis region but is still within the abdominal cavity, such as the surface of the intestine or liver.
Stage IV: If one or both ovaries are involved and the tumour has spread outside the abdomen or has spread to the inside of the liver.
Autologous Dendritic Cell Potency to activate the naïve T− cells of Immune system to treat tumour related malignant diseases is a revolutionary medical treatment approach Immune system has the potential to eliminate neoplastic cells. Escape from immune surveillance is believed to be a fundamental biological feature of malignant disease in man, which contributes to uncontrolled tumour growth, eventually leading to death of the host. Defects in immune response in patients with a variety of tumours and in tumour-bearing animals have been well documented. The key element is the induction of the anti-cancer immune response, namely Tumor Associated Antigens (TAAg) presentation to T cells in a tumour-bearing host (human and animal). Bone marrow-derived Antigen Presenting Cells (APCs) were shown to play an important role in the presentation of TAAgs, a function previously assigned predominantly to tumour cells. Therefore, elucidation of the role of such APCs, in particular Dendritic Cells (DCs) helped to better understand the mechanisms underlying anti-tumour immune responses and, improve the effectiveness of anti-cancer immunity in tumour-bearing hosts.
Dendritic cells are Antigen Presenting Cells (APCs) which play a critical role in the regulation of the adaptive immune response. Dendritic cells (DCs) are unique and have been referred to as “professional” APCs. The principal function of DCs is to present antigens; only DCs have the ability to induce a primary immune response in resting naïve T lymphocytes. To perform this function, DCs capture antigens, process them, and present them on the cell surface along with appropriate co-stimulatory molecules. DCs also play a role in the maintenance of B cell function and recall responses. Thus, DCs are critical in the establishment of immunological memory. The unique ability of DCs to activate naïve and memory CD4+ and CD8+ T cells suggests that they could be used for the induction of a specific antitumour immunity. In the past few years, several in vitro and in vivo studies in rodents and humans have demonstrated that immunizations with DCs pulsed with tumour antigens resulted in protective immunity and rejection of established tumours in various malignancies.
Ovarian cancer precursors, originating from the bone marrow, migrate to virtually every organ in the body, where immature DCs take up the surrounding antigens. After antigen uptake, the DCs mature, co-stimulatory molecules (e.g., CD40, CD80, CD86) are up regulated and the DCs migrate to the lymphoid tissues where they activate effector T cells. Consequently, tumour antigen-loaded DCs may be ideal cells for the generation and amplification of antitumour responses in a vaccination setting. Several clinical studies have shown distinct clinical responses after vaccination with tumour antigen-loaded, autologous DCs. Despite these successes, the only problem remaining is limited number of DCs available for immunotherapy. As DCs are not only important for the initiation of specific cytotoxic T cell (CTL) responses, but also for the maintenance of protective CTL, it may be crucial to repeatedly vaccinate cancer patients with tumor antigen-loaded DCs. Studies reported that myeloid dendritic cells (mDCs) derived in vitro suppressed angiogenesis in vivo through production of interleukin 12, implicating the role of mDCs in tumour pathology. The therapeutic implications of recent findings state that specific myeloid cell populations of dendritic cells modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies.
Mesenchymal stem cells (MSCs) targeted to cancers are expected to contribute many soluble factors such as mitogens, extracellular matrix proteins, angiogenic and inflammatory factors, as well as exosomes with as yet poorly defined potentials, once resident in the Tumour Micro Environment (TME). MSCs are also expected to affect tumour-associated leukocytes either directly by cell-cell contact or indirectly by the secretion of trophic factors. MSCs are known to affect the proliferation and differentiation of dendritic cells, monocytes/macrophages, B and T cells, NK cells, and even mast cells. There has been a great deal of debate in the field in trying to assert the role of MSCs in anti-tumour mechanisms.
Ovarian cancer treatment usually involves surgery, chemotherapy and autologous dendritic cell therapy. The primary one is surgery at which time the cancer is removed from the ovary and from as many other sites as is possible. Chemotherapy is the second important modality which uses drugs to kill the cancer cells. The other modality is radiation treatment, which is used in only certain instances. It utilizes high energy x-rays to kill cancer cells. Second look surgery and Salvage chemotherapy are the other treatment options to address recurrent types of ovarian cancers. High-dose chemotherapy accompanied with Autologous Bone Marrow Transplantation (ABMT) and Peripheral Blood Stem Cell transplantation (PBSCT) produces high response rates (70-82%) in patients with resistance to primary chemotherapy, but the responses are generally of limited duration. Such approaches are generally limited to clinical trials, and are also being tested for first line therapy. Autologous dendritic cell therapy is being practiced as experimental personalized therapy addressing relapsed/refractory types. This service involves the patient's own immune system to kill the cancer cells. These immune cells are called dendritic cells that are monocytes and are harvested from patient's blood. The dendritic cells are cultured in a special classified laboratory, formulated into a vaccine using the patient's own tumour cells.
U.S. Pat. No. 7,414,108 entitled “Composition and method for producing an immune response against tumour-related antigens” discloses a novel composition and a method for producing an immune response that is directed against a tumour-related antigen. This invention uses mouse prostatic acid phosphatase (mPAP) which can be used as a xenogeneic antigen to induce prostate-directed immunity in other mammalian species. The vehicles that are used for this induction include viruses such as vaccinia virus or dendritic cells which express mPAP, human PAP or rat PAP.
U.S. Pat. No. 6,210,662 entitled “Immunostimulatory composition” discloses an invention which is directed to a therapeutic composition for stimulating a cellular immune response. The novel composition disclosed is an isolated, stimulated potent antigen presenting cell such as activated dendritic cell that can activate T-cells to produce a multivalent cellular immune response against a selected antigen. The potent antigen presenting cells are stimulated by exposing them in vitro to a polypeptide complex which is essentially of a dendritic cell-binding protein and a polypeptide antigen.
U.S. Pat. No. 6,194,152 entitled “Prostate tumour polynucleotide compositions and methods of detection thereof” provides chimeric polypeptide molecules comprising the polypeptides fused to heterologous polypeptide sequences, and antibodies which bind to the polypeptides. It also provides a method for producing the polypeptides disclosed above, as are detection assays that detect the presence of tumour cells in tissue or bodily fluid samples and a method for identifying novel compositions which modulate the activity of prostate tumour antigens and the use of such compositions in diagnosis and treatment of disease.
US Patent Application 20100055076 entitled “Mesenchymal stem cell-mediated autologous dendritic cells with increased immune suppression” describes a pharmaceutical composition comprising the dendritic cells capable of inducing immunosuppressive responses that has an enhanced potential to suppress immune responses can be utilized for treating various diseases.
The composition as disclosed in the present invention was prepared/adopted in treating the tumour has always been for autologous applications with autologous preparations and compositions. The dendritic cells were postulated to target the tumours with loaded antigens and there are not many global groups working on dendritic cell vaccines which adopt the properties of mesenchymal stem cells for ovarian cancer treatment. Allogenic dendritic cells—mesenchymal stem cells combination (Mesendritic) as the vector in targeted ovarian cancer treatment is innovative concept in cancer therapeutics.